Systematic, opt-out HIV counselling and testing (HCT) may diagnose individuals at lower levels of immunodeficiency but may impact loss to follow-up (LTFU) if healthier people are less motivated to engage and remain in HIV care. We explored LTFU and patient clinical outcomes under two different HIV testing strategies.

Magnetic resonance imaging (MRI) is a potentially ideal imaging modality for noninvasive, nonionizing, and longitudinal assessment of disease. Hyperpolarized (HP) agents have been developed in the past 20 years for MR imaging, and they have the potential to vastly improve MRI sensitivity for the diagnosis and management of various diseases. The polarization of nuclear magnetic resonance (NMR)-sensitive nuclei other than (1)H (e.g., (3)He, (129)Xe) can be enhanced by a factor of up to 100,000 times above thermal equilibrium levels, which enables direct detection of the HP agent with no background signal. In this review, a number of HP media applications in MR imaging are discussed, including HP (3)He and (129)Xe lung imaging, HP (129)Xe brain imaging, and HP (129)Xe biosensors. Inert fluorinated gas MRI, which is a new lung imaging technique that does not require hyperpolarization, is also briefly discussed. This technique will likely be an important future direction for the HP gas lung imaging community.

HIV-exposed uninfected infants are an increasing population. Past analyses have often categorized these infants as uninfected leading to inaccurate conclusions. We present a HIV exposure, rather than infection, based reanalysis of treatment failure among children with pneumonia to show that failure odds among HIV-exposed uninfected infants are intermediate between their unexposed and infected counterparts. Additional prospective studies aimed at better understanding this population are needed.

High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.

Inert fluorinated gas lung MRI is a new and promising alternative to hyperpolarized gas lung MRI; it is less expensive and does not require expensive isotopes/polarizers. The thermally polarized nature of signal obtained from fluorinated gases makes it relatively easy to use for dynamic lung imaging and for obtaining lung ventilation maps. In this study, we propose that the sensitivity and resolution of fluorine-19 ((19) F) in vivo images can be improved using the x-centric pulse sequence, thereby achieving a short echo time/pulse repetition time. This study is a transitional step for converting to more sustainable gases for lung imaging.

Quantitative bias analysis serves several objectives in epidemiological research. First, it provides a quantitative estimate of the direction, magnitude and uncertainty arising from systematic errors. Second, the acts of identifying sources of systematic error, writing down models to quantify them, assigning values to the bias parameters and interpreting the results combat the human tendency towards overconfidence in research results, syntheses and critiques and the inferences that rest upon them. Finally, by suggesting aspects that dominate uncertainty in a particular research result or topic area, bias analysis can guide efficient allocation of sparse research resources. The fundamental methods of bias analyses have been known for decades, and there have been calls for more widespread use for nearly as long. There was a time when some believed that bias analyses were rarely undertaken because the methods were not widely known and because automated computing tools were not readily available to implement the methods. These shortcomings have been largely resolved. We must, therefore, contemplate other barriers to implementation. One possibility is that practitioners avoid the analyses because they lack confidence in the practice of bias analysis. The purpose of this paper is therefore to describe what we view as good practices for applying quantitative bias analysis to epidemiological data, directed towards those familiar with the methods. We focus on answering questions often posed to those of us who advocate incorporation of bias analysis methods into teaching and research. These include the following. When is bias analysis practical and productive? How does one select the biases that ought to be addressed? How does one select a method to model biases? How does one assign values to the parameters of a bias model? How does one present and interpret a bias analysis?. We hope that our guide to good practices for conducting and presenting bias analyses will encourage more widespread use of bias analysis to estimate the potential magnitude and direction of biases, as well as the uncertainty in estimates potentially influenced by the biases.

Radiation induced lung injury (RILI) is a common side effect for patients undergoing thoracic radiation therapy (RT). RILI can lead to temporary or permanent loss of lung function and in extreme cases, death. Combining functional lung imaging information with conventional radiation treatment plans may lead to more desirable treatment plans that reduce lung toxicity and improve the quality of life for lung cancer survivors. Magnetic Resonance Imaging of the lung following inhalation of hyperpolarized(129)Xe may provide a useful nonionizing approach for probing changes in lung function and structure associated with RILI before, during, or after RT (early and late time-points).

Little is known about outcomes after transfer out (TFO) and loss to follow-up (LTF) and how differential outcomes might bias mortality estimates, as analyses generally censor or exclude TFOs/LTF. Using data linked to the National Population Register, we explored mortality among TFO and LTF patients compared with patients who were retained and investigated how linkage impacted on mortality estimates.

The aim of this study was to determine T2* values for the fetal brain in utero and to compare them with previously reported values in preterm and term neonates. Knowledge of T2* may be useful for assessing brain development, brain abnormalities, and for optimizing functional imaging studies.

To describe the characteristics of HIV-infected patients experiencing herpes zoster after antiretroviral therapy (ART) initiation and to describe the incidence and predictors of a herpes zoster diagnosis.

The incidence of Kaposi's Sarcoma (KS) is high in South Africa but the impact of antiretroviral therapy (ART) is not well defined. We examined incidence and survival of KS in HIV-infected patients enrolled in South African ART programs. We analyzed data of three ART programs: Khayelitsha township and Tygerberg Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We included patients aged >16 years. ART was defined as a regimen of at least three drugs. We estimated incidence rates of KS for patients on ART and not on ART. We calculated Cox models adjusted for age, sex and time-updated CD4 cell counts and HIV-1 RNA. A total of 18,254 patients (median age 34.5 years, 64% female, median CD4 cell count at enrolment 105 cells/?L) were included. During 37,488 person-years follow-up 162 patients developed KS. The incidence was 1,682/100,000 person-years (95% confidence interval [CI] 1,406-2,011) among patients not receiving ART and 138/100,000 person-years (95% CI 102-187) among patients on ART. The adjusted hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13-0.28). Low CD4 cell counts (time-updated) and male sex were also associated with KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9-80.2) and higher in men than in women. The incidence of KS is substantially lower on ART than not on ART. Timely initiation of ART is essential to prevent KS and KS-associated morbidity and mortality in South Africa and other regions in Africa with a high burden of HIV.

There is growing interest in exploring fetal functional brain development, particularly with Resting State fMRI. However, during a typical fMRI acquisition, the womb moves due to maternal respiration and the fetus may perform large-scale and unpredictable movements. Conventional fMRI processing pipelines, which assume that brain movements are infrequent or at least small, are not suitable. Previous published studies have tackled this problem by adopting conventional methods and discarding as much as 40% or more of the acquired data. In this work, we developed and tested a processing framework for fetal Resting State fMRI, capable of correcting gross motion. The method comprises bias field and spin history corrections in the scanner frame of reference, combined with slice to volume registration and scattered data interpolation to place all data into a consistent anatomical space. The aim is to recover an ordered set of samples suitable for further analysis using standard tools such as Group Independent Component Analysis (Group ICA). We have tested the approach using simulations and in vivo data acquired at 1.5 T. After full motion correction, Group ICA performed on a population of 8 fetuses extracted 20 networks, 6 of which were identified as matching those previously observed in preterm babies.

Previous research has raised concerns that patients given nevirapine (NVP)-based regimens experience more virologic failure than patients given efavirenz (EFV)-based regimens. We investigated this hypothesis in a cohort of HIV-positive patients at a large HIV treatment clinic in South Africa.

While momentum for increasing treatment thresholds is growing, if patients cannot be retained in HIV care from the time of testing positive through long-term adherence to antiretroviral therapy (ART), such strategies may fall short of expected gains. While estimates of retention on ART exist, few cohorts have data on retention from testing positive through long-term ART care.

Several studies from resource-limited settings have demonstrated that clinical and immunologic criteria are poor predictors of virologic failure, confirming the need for viral load monitoring or at least an algorithm to target viral load testing. We used data from an electronic patient management system to develop an algorithm to identify patients at risk of viral failure using a combination of accessible and inexpensive markers.

Voice recognition (VR) technology needs improvement, but is as integral to the current practice of radiology as Radiology Information Systems and Picture Archival and Communication Systems. In the 1990s, the radiology community gave VR technology a rather lukewarm reception, but since then it has emerged as the predominant method of radiology reporting in the United States. In this article, we examine how VR technology works, outline the positive and negative aspects of VR technology on work flow, identify common VR transcription errors and review the discussion on VR adoption in the recent literature. We add to the discussion our personal experiences in an international teleradiology group.

There is debate over using tenofovir or zidovudine alongside lamivudine in second-line antiretroviral therapy (ART) following stavudine failure. We analyzed outcomes in cohorts from South Africa, Zambia and Zimbabwe METHODS: Patients aged ?16 years who switched from a first-line regimen including stavudine to a ritonavir-boosted lopinavir-based second-line regimen with lamivudine or emtricitabine and zidovudine or tenofovir in seven ART programs in southern Africa were included. We estimated the causal effect of receiving tenofovir or zidovudine on mortality and virological failure using Cox proportional hazards marginal structural models. Its parameters were estimated using inverse probability of treatment weights. Baseline characteristics were age, sex, calendar year and country. CD4 cell count, creatinine and hemoglobin levels were included as time-dependent confounders.

Patients with epidermolysis bullosa (EB) do not carry a significantly increased risk of melanoma but are prone to developing large, markedly atypical melanocytic nevi (EB nevi), which may mimic melanoma clinically and histologically. Many authors now favor a conservative approach in managing atypical pigmented lesions in patients with EB.

In August 2011, South Africa expanded its adult antiretroviral therapy (ART) guidelines to allow treatment initiation at CD4 cell values 350?cells/?l or less. Mortality and morbidity are known to be reduced when initiating at higher CD4 levels; we explored the impact on patient loss to follow-up.

Few studies have compared hospitalizations before and after antiretroviral therapy (ART) initiation in the same patients. We analyzed the cost of hospitalizations among 3906 adult patients in 2 South African hospitals, 30% of whom initiated ART. Hospitalizations were 50% and 40% more frequent and 1.5 and 2.6 times more costly at a CD4 cell count, 100 cells/mm(3) when compared with 200–350 cells/mm(3) in the pre-ART and ART period, respectively. Mean inpatient cost per patient year was USD 117 (95%confidence interval, 85 to 158) for patients on ART and USD 72(95% confidence interval, 56 to 89) for pre-ART patients. Raising ART eligibility thresholds could avoid the high cost of hospitalization before and immediately after ART initiation.

South African HIV care providers are exploring ways to reduce the intensity of patient visits while maintaining high quality of care. We used routinely collected data to model whether a simple screening tool could identify stable patients who would not need to see a doctor during a scheduled medical visit.

Acute hemorrhagic leukoencephalopathy (AHLE) is a rare condition associated with H1N1. In this condition the infection triggers an autoimmune response which results in perivascular demyelination and hemorrhage in the brain parenchyma.

Introduction: In April 2010, tenofovir replaced stavudine in public-sector first-line antiretroviral therapy (ART) in South Africa. The association of tenofovir with fewer side effects and toxicities compared to stavudine could translate to increased durability of tenofovir-based regimens. We evaluated changes over time in regimen durability at the Themba Lethu Clinic, Johannesburg, South Africa. Methods: This was a cohort analysis of treatment-naïve, non-pregnant adult patients initiated on ART between April 2004 and December 2011. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir was substituted for stavudine after April 2010. We evaluated the frequency and type of single-drug substitutions (excluding switches to second-line therapy). Cox models were used to evaluate the association of ART initiation year and antiretroviral drug type with single-drug substitutions in the first 12 months on treatment. Results: One thousand nine hundred and sixty-four (10%) substitutions occurred amongst 19,699 patients. Excluding 2004 (year of treatment roll-out), before 2010 one-year single-drug substitutions ranged from 10.0 to 13.1%. In 2011, well after integration of tenofovir, substitutions decreased to 5.6%. Single-drug substitution was lowest amongst patients on tenofovir (5.1%) versus zidovudine (11.3%), 30 mg stavudine (10.5%) or 40 mg stavudine (14.4%). Adjusted Cox models showed that patients initiating treatment between 2005 and 2010 (vs. 2011) had a twofold increased hazard of single-drug substitution, while those on zidovudine or stavudine had a two to threefold increase in single-drug substitution versus tenofovir patients in the first 12 months on ART. Conclusions: The decline in single-drug substitutions is associated with the introduction of tenofovir. Tenofovir use could improve regimen durability and treatment outcomes in resource-limited settings.

To estimate the impact of antiretroviral therapy (ART) on labor productivity and income using detailed employment data from two large tea plantations in western Kenya for HIV-infected tea pluckers who initiated ART.

The possible impact of coinfection with the Kaposi sarcoma-associated herpes virus (KSHV) on the response to antiretroviral therapy (ART) is unknown. Prospective studies are rare, particularly in Africa.

Fetal magnetic resonance imaging (MRI) is now routinely used to further investigate cerebellar malformations detected with ultrasound. However, the lack of 2D and 3D biometrics in the current literature hinders the detailed characterisation and classification of cerebellar anomalies. The main objectives of this fetal neuroimaging study were to provide normal posterior fossa growth trajectories during the second and third trimesters of pregnancy via semi-automatic segmentation of reconstructed fetal brain MR images and to assess common cerebellar malformations in comparison with the reference data. Using a 1.5-T MRI scanner, 143 MR images were obtained from 79 normal control and 53 fetuses with posterior fossa abnormalities that were grouped according to the severity of diagnosis on visual MRI inspections. All quantifications were performed on volumetric datasets, and supplemental outcome information was collected from the surviving infants. Normal growth trajectories of total brain, cerebellar, vermis, pons and fourth ventricle volumes showed significant correlations with 2D measurements and increased in second-order polynomial trends across gestation (Pearson r, p?0.05). Comparison of normal controls to five abnormal cerebellum subgroups depicted significant alterations in volumes that could not be detected exclusively with 2D analysis (MANCOVA, p?0.05). There were 15 terminations of pregnancy, 8 neonatal deaths, and a spectrum of genetic and neurodevelopmental outcomes in the assessed 24 children with cerebellar abnormalities. The given posterior fossa biometrics enhance the delineation of normal and abnormal cerebellar phenotypes on fetal MRI and confirm the advantages of utilizing advanced neuroimaging tools in clinical fetal research.

Background. We evaluated whether a pilot program providing point-of-care (POC), but not rapid, CD4 testing (BD FACSCount) immediately after testing HIV-positive improved retention in care. Methods. We conducted a retrospective record review at the Themba Lethu Clinic in Johannesburg, South Africa. We compared all walk-in patients testing HIV-positive during February, July 2010 (pilot POC period) to patients testing positive during January 2008-February 2009 (baseline period). The outcome for those with a ?250 cells/mm(3) when testing HIV-positive was initiating ART <16 weeks after HIV testing. Results. 771 patients had CD4 results from the day of HIV testing (421 pilots, 350 baselines). ART initiation within 16 weeks was 49% in the pilot period and 46% in the baseline period. While all 421 patients during the pilot period should have been offered the POC test, patient records indicate that only 73% of them were actually offered it, and among these patients only 63% accepted the offer. Conclusions. Offering CD4 testing using a point-of-care, but not rapid, technology and without other health system changes had minor impacts on the uptake of HIV care and treatment. Point-of-care technologies alone may not be enough to improve linkage to care and treatment after HIV testing.

Our group has previously demonstrated that expression of the cytokine stem cell factor (SCF) by leukemic blasts is a frequent finding in pre-B acute lymphoblastic leukemia (ALL). Whether SCF expression is a feature of other B cell malignancies and whether cross-talk from the local microenvironment modulates malignant cell SCF production are, however, unknown. Here we show using immunohistochemistry that SCF is expressed by a wide variety of indolent and aggressive B cell malignancies involving the bone marrow (BM) or lymph nodes (LNs). In diseases such as follicular lymphoma (FL), however, where lymphoma cells uniquely associate with the BM endosteal niche, BM lymphoma does not express SCF, while LN involvement is SCF positive. In contrast, cases of FL with high-grade transformation in the BM are SCF positive. These data suggest that lymphoma cell interaction with the endosteal niche inhibits SCF production, and that FL cells become independent of this microenvironment effect following transformation.

Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults.

Part II of this continuing medical education article will discuss the treatment options for stage IV melanoma, including novel therapies, such as ipilimumab and vemurafenib; established therapies, including high-dose interleukin-2, conventional chemotherapy, and biochemotherapy; and additional therapies currently under investigation in the form of clinical trials. The approach to patients with brain metastases will be discussed, as will recommendations for distress screening and defining aspects of palliative care.

The incidence of melanoma has increased for decades, and while surgical treatment of early stage disease is often curative, metastatic disease continues to carry a significantly less promising outlook with high associated health burden and economic cost. An expanding number of dermatologists are playing a key role in coordinating the care of patients with melanoma, including in an increasingly important role among multidisciplinary melanoma clinics, many of which are anchored in dermatology departments. Advances in the understanding of the genetic and immunoregulatory aspects of melanoma development and progression have yielded a wave of novel therapeutics that has made significant impact on the approach to patients with metastatic disease. Frequently updated management guidelines and unfamiliarity with approved adjuvant treatment options, including interferon, clinical trials, or radiation therapy, can pose a challenge for dermatologists seeking to effectively coordinate the care of and establish proper expectations for patients with stage III disease. Moreover, greater awareness of treatment modalities for in-transit disease may allow dermatologists to play a more active role in the treatment of these patients and to expand their ability to explain and coordinate options, such as limb perfusion or infusion. Part I of this continuing medical education article will use clinical scenarios to outline the current management options for patients with stage III melanoma, including both adjuvant treatment options for resected stage III disease and primary treatment options for in-transit metastases. Part II of this series will address stage IV disease.

In many resource-limited settings monitoring of combination antiretroviral therapy (cART) is based on the current CD4 count, with limited access to HIV RNA tests or laboratory diagnostics. We examined whether the CD4 count slope over 6 months could provide additional prognostic information.

Recent WHO guidelines for resource-limited settings recommend tenofovir in first-line antiretroviral therapy (ART) yet there are suggestions that patients receiving nevirapine with tenofovir have worse outcomes than those receiving efavirenz. We sought to compare outcomes among those taking nevirapine vs. efavirenz with tenofovir and lamivudine.

Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART.

First dose oral co-trimoxazole and referral are recommended for WHO-defined severe pneumonia. Difficulties with referral compliance are reported in many low-resource settings, resulting in low access to appropriate treatment. The objective in this study was to assess whether community case management by lady health workers (LHWs) with oral amoxicillin in children with severe pneumonia was equivalent to current standard of care.

To compare clinical, immunologic and virologic outcomes among stable HIV-positive patients down-referred to a nurse-managed primary healthcare clinic (PHC) for treatment maintenance to those who remained at a doctor-managed treatment-initiation site.

Kaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV) infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART) and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV.

In April 2010, the South African government added tenofovir disoproxil fumarate to its first-line antiretroviral therapy (ART) for HIV patients. We analyzed the relationship between renal dysfunction at tenofovir initiation, nephrotoxicity and mortality.

The emergence of complex HIV-1 drug resistance mutations has been linked to the duration of time patients are on a failing antiretroviral drug regimen. This study reports on resistance profiles in a closely monitored subtype C infected cohort.

Current guidelines for providing antiretroviral therapy (ART) in South Africas public sector programme call for switching patients from first-line to second-line treatment upon virologic failure as indicated by two consecutive viral loads above 5000 copies/ml, but without laboratory evidence of viral resistance. We modelled the net cost of adding resistance testing for patients with virological failure and retaining patients without resistance on first-line therapy, rather than switching all failures to second-line therapy.

A recent randomized clinical trial demonstrated home-based treatment of WHO-defined severe pneumonia with oral amoxicillin was equivalent to hospital-based therapy and parenteral antibiotics. We aimed to determine whether this finding is generalizable across four countries.

To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a resource poor country with limited access to healthcare.

The World Health Organization estimates that in sub-Saharan Africa about 4 million HIV-infected patients had started antiretroviral therapy (ART) by the end of 2008. Loss of patients to follow-up and care is an important problem for treatment programmes in this region. As mortality is high in these patients compared to patients remaining in care, ART programmes with high rates of loss to follow-up may substantially underestimate mortality of all patients starting ART.

Adherence to care and treatment are essential for HIV-infected individuals to benefit from antiretroviral therapy (ART). We sought to quantify the effects on treatment outcomes of missing visits soon after initiating ART.

Little is known about the temporal impact of the rapid scale-up of large antiretroviral therapy (ART) services on programme outcomes. We describe patient outcomes [mortality, loss-to-follow-up (LTFU) and retention] over time in a network of South African ART cohorts.

Regional measurement of alveolar oxygen partial pressure can be obtained from the relaxation rates of hyperpolarized noble gases, (3) He and (129) Xe, in the lungs. Recently, it has been demonstrated that measurements of alveolar oxygen partial pressure can be obtained using the spin-spin relaxation rate (R(2) ) of (3) He at low magnetic field strengths (<0.1 T) in vivo. R(2) measurements can be achieved efficiently using the Carr-Purcell-Meiboom-Gill pulse sequence. In this work, alveolar oxygen partial pressure measurements based on Carr-Purcell-Meiboom-Gill R(2) values of hyperpolarized (3) He and (129) Xe in vitro and in vivo in the rat lung at low magnetic field strength (74 mT) are presented. In vitro spin-spin relaxivity constants for (3) He and (129) Xe were determined to be (5.2 ± 0.6) × 10(-6) Pa(-1) sec(-1) and (7.3 ± 0.4) × 10(-6) Pa(-1) s(-1) compared with spin-lattice relaxivity constants of (4.0 ± 0.4) × 10(-6) Pa(-1) s(-1) and (4.3 ± 1.3) × 10(-6) Pa(-1) s(-1), respectively. In vivo experimental measurements of alveolar oxygen partial pressure using (3) He in whole rat lung show good agreement (r(2) = 0.973) with predictions based on lung volumes and ventilation parameters. For (129) Xe, multicomponent relaxation was observed with one component exhibiting an increase in R(2) with decreasing alveolar oxygen partial pressure.

WO3(4,4-bipyridyl)0.5 was doped with Na+ by ion implantation so as to alter the electronic structure. Single-crystal X-ray diffraction reveals layers of corner-shared WO5N octahedra linked by bipyridine. In the observed space group of Pbca, the fully-ordered bipyridyls form cages with Na+ disordered bimodally about the cage centre.

Although the medical outcomes of antiretroviral therapy (ART) for HIV/AIDS are well described, less is known about how ART affects patients economic activities and quality of life, especially after the first year on ART. We assessed symptom prevalence, general health, ability to perform normal activities, and employment status among adult antiretroviral therapy patients in South Africa over three full years following ART initiation.

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